Controlled and prolonged release of pharmacologically active (hereafter "pharmacological") compounds is known in the art and described in many patents. Most of these patents, however, deal with release of low molecular weight compounds. Release of macromolecular compounds has been problematic due to difficulties inherent in such release. Thus, macromolecular compounds do not diffuse as easily through the matrix in which they are contained and they tend to be susceptible to deactivation during preparation of the delivery device and during release from the device, e.g. polypeptides and proteins are denatured.
U.S. Pat. No. 4,164,560 describes release of a macromolecular drug from a matrix of biocompatible polymer that remains substantially intact throughout the release of the drug. European Pat. Publication No. 92,918 discloses sustained release of pharmacologically active polypeptides copolymer having a hydrophobic and hydrophilic component. Neither reference includes chitosan as a possible matrix.
Miyazaki et al., Chem. Pharm. Bull. 29 (10), 3067-3069 (1981) suggest chitin and chitosan for sustained release of drugs. However, only the low molecular weight drugs indomethacin and papaverine hydrochloride are mentioned. Macromolecular drugs are clearly not considered. Similarly Sawayanagi et al., Chem Pharm. Bull., 39 (11), 4213-4215 (1982) describe sustained release of a low molecular weight drug, propranolol hydrochloride, from chitosan.